Small study found most patients helped by ziprasidone

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The antipsychotic drug ziprasidone could help in treating debilitating migraine lasting more than 72 hours in patients who don't respond to other treatments, according to a retrospective chart review of 43 patients.

Note that prior studies with neuroleptics droperidol and haloperidol showed a comparable therapeutic response though ziprasidone may have a better side effect profile.

BALTIMORE -- The antipsychotic drug ziprasidone could be helpful in treating lasting migraines among patients who don't respond to other treatments, according to research presented here.

In a retrospective chart review of 43 patients who had a debilitating migraine lasting more than 72 hours who were given 10 to 40 mg of ziprasidone as a third-line agent, the drug was helpful 81% of the time and definitively led to hospital discharge in 65% of patients, said lead study author Eric Landsness, MD, PhD, a fourth-year neurology resident at Washington University School of Medicine/Barnes-Jewish Hospital.

The drug is approved by the Food and Drug Administration for the treatment of schizophrenia, and acute mania and mixed states associated with bipolar disorder.

"I think this has potential for being the next atypical antipsychotic used for the treatment of status migrainous," Landsness told MedPage Today. While the study is observational, he said this falls under one of the "three or four moments in my life where I look at something and say, 'This really works.' You can't explain this away with [a] placebo [effect]."

Landsness said 2 years ago he treated a woman who had traveled to Barnes-Jewish Hospital from Iowa saying she had been on 30 medications and nothing was helping. While some physicians use Haldol, he decided to look at something in the same category that causes fewer side effects.

He gave the patient an intramuscular injection of ziprasidone and the next morning she reported sleeping like a log. "She said she had the best sleep in her life and her headache was gone. She hugged me and walked out the door." The experience got him curious about other patients' experiences with ziprasidone.

He reviewed patient charts from 2007 to 2015 looking for patients given ziprasidone as a third-line treatment for migraine. The patients, 84% of whom were female, were pre-menopausal (average 39). The majority (80%) were white, 16% were African American and 4% were unknown. More than half (57%) had prior hospital admissions for migraine; the median migraine duration was 17.5 days. Eighty-seven percent had photophobia or phonophobia, 80% had nausea/emesis, and 40% had aura. In other variables, 36% had prior head trauma; 46% had psychiatric disease; 48% had caffeine use; 41% had sleep problems; 31% had a family history of migraine; and 70% had work impairment.

On average, patients were given 4.7 ± 2.5 different types of medications before ziprasidone. The average hospital length of stay was 3 ± 2 days.

Looking at outcomes among 34 of the patients, headache severity decreased from 9.01 ± 1.04 to 3.3 ± 3.0 on the Visual Analog Scale for Pain. The drug was well tolerated, with side effects limited to a mild dystonic reaction (2%), rhinorrhea (2%) and a prolonged corrected QT interval (2%). The 30-day readmission rate was 12%.

"We're noticing that not only do patients feel better but they also leave the hospital faster," Landsness said. "They're leaving a day earlier than we did before so I see this as a huge chance if we could start using this as first-line therapy, even down in the emergency department, we could cut down on headache admission cost."

To put the findings in the context of headache literature, Landsness and colleagues compared the work to two prior studies using the neuroleptics droperidol and haloperidol. All three studies showed a comparable therapeutic response though ziprasidone may have a better side effect profile than the others, Landsness said.

"I don't think you can make any major conclusions about treatment on this because it's just retrospective and so it's biased toward people who were refractory," Laurie Gutmann, MD, a clinical professor of neurology at the University of Iowa Carver College of Medicine and poster judge, told MedPage Today. "To say that this is a new treatment ... is too premature." However, many patients with status migrainous are turning up in emergency rooms, she said, and ERs without neurologists might use opioids. "We know that's probably the worst thing to use because it just causes patients to bounce back. It helps their headache and they come right back." [Ziprasidone] is abortive by fighting the D2 receptor, she said, "It's a nice longer term way of stopping the headache and getting people back into the workforce etc."

The study was funded by grants from the Washington University Institute of Clinical and Translational Sciences and the National Institutes of Health's National Center for Advancing Translational Sciences.

Landsness and Gutmann disclosed no relevant relationships with industry.

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